Objective: The main goal of this article is
to highlight gender-specific differences in the
epidemiology, clinical nature, and treatment
responses of comorbid depression and substance abuse.
The second goal is to make recommendations for future research in the area of gender-specific
aspects of comorbid depression and substance abuse.

Data Synthesis: A literature review was
conducted using the keywords sex, gender, depression, and substance use
disorders for the time period 1980 to the present. We first outline
the well-known sex differences in the epidemiology of depressed substance abusers and discuss
the clinical significance of substance abuse in
depression. Two distinct ways of understanding the
role of substance abuse in depression are
presented. The first is the role that depression may play
in escalation of substance use, and the second is depression as a common sequela of chronic
substance abuse. These 2 manifestations that are
not mutually exclusive, often co-occurring in
female substance abusers, have important treatment
implications. Research on treatment response for
the above clinical presentations is discussed
followed by a summary of the factors that may
influence sex differences in the association between
depression and substance abuse.

Conclusion: Recommendations for future
research examining sex differences in animal models of depression, substance abuse, and
therapeutic response to medications were made. The
need for gender-specific clinical research on the
association between depression, stress, and
substance abuse is also highlighted.